Side-effects analysis reveals new uses for old drugs

时间：2019-03-01 08:18:00166网络整理admin

By Ewen Callaway Unexpected drug side effects run from bothersome headaches to catastrophic heart attacks, and even suicides. But by connecting the dots between the common side effects of different drugs, scientists might give new life to old medicines, a new study suggests. Researchers compared the side effects of 746 drugs with the premise that drugs with similar symptoms might incidentally affect the same proteins. Mining the information on warning labels could also make for cheaper and safer drugs, says Peer Bork, a computational biologist at the European Molecular Biology Laboratory in Heidelberg, Germany, who led the study. Among hundreds of pharmaceutical surprises, his team discovered that a stomach ulcer drug also tweaks a molecular sensor for dopamine, a key brain chemical that’s reduced in Parkinson’s disease. Unwanted but unavoidable, side effects are a way of life for the drug industry. Chemicals built for one job usually meddle elsewhere. Antidepressants such as Prozac and Zoloft may battle depression by making more serotonin available to the brain, but they can also cause insomnia and dampen sex drive. Sometimes such surprises turn into goldmines. Sildenafil (Viagra) was first developed to treat a type of chest condition called angina, until users noticed a peculiar side effect that has since reinvigorated the sex lives of millions of impotent men. In search of a less serendipitous way to uncover such beneficial side effects, Bork and his colleagues sifted through warning labels of 746 drugs – basically admonitions of headache, nausea, dizziness and other symptoms that people hopefully glance over before popping a pill. The researchers compared these government-required warnings with a database of the proteins the drugs were designed to target, and then drew lines between targets and symptoms. The result was a list of nearly 3,000 pairs of drugs with similar side effects that targeted the same protein. Many of these were known, but Bork’s team say 261 of them are surprises. For instance, a drug that treats ulcers by blocking cells from spewing acidic molecules into the stomach also blocks the same brain cell receptors as a pill that eases symptoms of Parkinson’s disease. Bork’s team confirmed this link in test tubes and in living cells. “You could use this kind of stomach ulcer drug and look whether it has an impact on Parkinson’s or Alzheimer’s,” he speculates. Lab tests on another 20 predictions confirmed 13 surprising links, including a brain-boosting Alzheimer’s drug that might combat depression. However, his list should also reveal unknown side effects of existing meds. Discovering new uses for drugs might also slash costs because the drugs have already been proven to be safe in costly clinical trials, Bork says. Tests in animals and eventually in humans for effectiveness will be needed before any of drugs can be marketed for such novel uses. But physicians in many countries, including the US and Britain, can prescribe drugs for such “off-label” uses. Bork warns that doctors should not use the predictions to discover off-label uses, however. Yet drug company culture, which usually divides research into disease-specific areas such as cancer and heart disease, might impede new applications, says Bork, who has previously launched four biotechnology companies. Atul Butte, a computational biologist at Stanford University Medical School in California, says it will take time for computer predictions of new drug uses find their way to the medicine cabinet. “We’re used to doing genomics and informatics at internet speed. The minute it leaves the computer, it enters regulatory speed,” he says. Journal reference: Science (DOI: